Candidate - Dr. Lerner is a pediatric hematologist/oncologist who has recently redirected her focus to patient-oriented investigation. She has completed the course work for an MPH degree and has established working relationships with experienced clinical investigators at the University of Rochester Medical Center. Environment -The Medical Center has the experienced clinical researchers and requisite resources to ensure Dr. Lerner's success. In particular, a Consultant Committee will provide support for this proposal. The Clinical Trials Coordinating Center and Strong Children's Research Center will lend additional expertise. Research - Neurologic complications secondary to cerebrovascular disease are prevalent in children with homozygous sickle cell disease. It is hypothesized that daily low-dose aspirin therapy will safely diminish the incidence and progression of cognitive deficit as well as the predisposition to overt and silent stroke in these children. In order to maximize the design of a future Phase III trial to test this hypothesis, a pilot study has been approved by the NINDS. Its primary objective is to evaluate the safety and tolerability of aspirin. This K24 application proposes additional studies to augment the trial. These will investigate the prognostic relationship of laboratory markers of inflammation and coagulation to the incidence and progression of cerebrovascular damage. Subsequent investigations will evaluate the change secondary to aspirin therapy in those laboratory parameters with prognostic capability. Later proposed studies include investigations regarding magnetic resonance imaging in children with documented stroke on chronic transfusion therapy and tailored educational modifications to improve performance in children with neurocognitive deficits. Mentorship -The principle investigator will provide clinical research training to qualified MDs with a particular interest in pediatric cerebrovascular disease, hemoglobinopathies, and/or neurocognitive function. Trainees will be recruited from: Pediatric Hematology/Oncology fellows, Masters in Public Health (clinical track) candidates, participants in programs of the Department of Neurology, and residents. The program will include core educational instruction, seminar series, and individualized guidance. Trainees will participate in the conduct of the pilot trial and a multi-center phase III study, should this be funded. The additional studies proposed in this application will serve as initial individual clinical research opportunities. Outcome measures will be used to assess the efficacy of the mentoring program.